Aromatic and heteroaromatic units are important and pervasive structural motifs in molecules, both natural and artificial, that exhibit biological activity. Arene and heteroarene containing molecules are typically prepared using traditional synthetic approaches or biosynthesis. For traditional, and to a certain extent, biosynthetic feedstocks, the parent structures are typically the most abundant forms, and more complex analogs can be obtained through their direct functionalization. Electrophilic aromatic substitution (EAS) is most often called upon to effect such functionalizations. Herein, useful complement to EAS, namely direct functionalizations of sp2-hybridized arene and/or heteroarene C[unreadable]H bonds, are proposed. In this proposal specific solution is the catalytic dehydrogenative coupling of borane B[unreadable]H and sp2 C[unreadable]H bonds invented in the Smith laboratories at Michigan State University. The following Specific Aims will be addressed: 1. Mechanistic Studies. A unified experimental and computational approach is being designed to elucidate mechanistic features of C[unreadable]H borylation. Findings will be used to optimize existing catalysts and designing new catalysts. 2. Catalyst Design. Guided in part by the mechanistic studies in Specific Aim 1, catalyst modifications will be made to (a) improve discrimination between groups with similar steric requirements, (b) enhance reactivities of electron-rich substrates, (c) discriminate between electron-rich and electron-deficient ring systems when both are present, and (d) explore to potential for stereoselective C[unreadable]H borylation. 3. Borylations in Complex Systems. The complexity of molecular architectures that can both be operated upon and constructed by a particular reaction ultimately determines its impact as a synthetic method. With this in mind, C[unreadable]H borylation will be applied to (a) functionalization of selected biologically active molecules, most of which are commercially available, (b) elaboration of a protected tripeptide en route to a functional core of TMC- 95A, and (c) total syntheses of autolytimycin and (+)-isoplagiochin C and D.